Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be subdivided into internal physiological and pathological and external exogenous factors as. Ultimately, the expression of an enzyme, and therefore, the responses to drugs that it metabolizes will be an integration of all the nongenetic factors that can control the enzyme impinged upon the individuals genetic constitution. Factors affecting the renal excretion of drugs hall, stephen d. Factors affecting urinary excretion of testosterone metabolites conjugated with cysteine andreu fabregat bioanalysis research group, imim, hospital del mar, 08003 barcelona, spain. Drugrelated factors affecting pharmacokinetics the physicochemical properties of a drug, including its solubility and permea bility, affect its absorption. Factors affecting urinary excretion of testosterone. The renal excretion of drugs is mainly controlled by three factors. Factors affecting drug metabolism online lecture lecturio. Membrane structure and function the cell membrane is a semipermeable lipoid sieve containing numerous aqueous channels, as well as a variety of specialized carrier molecules. A combination of metabolism and excretion constitutes drug elimination from the body. The factors affecting absorption of drugs are related both to the drugs and to the body. Factors affecting renal excretion of drugs include.
Inhalation volatile anesthetics, as well as many drugs which affect pulmonary function, are administered as aerosols. Factors affecting distribution of drug tissue permeability of drug 1. Excretion of unchanged or intact drug is needed in termination of its pharmacological action. Possible factors affecting this stage include the rate of blood flow perfusion to the tissue, the tissue mass itself, and vascular and tissue membrane permeability. Drugs that are bound to large proteins in the plasma cannot be filtered out of the plasma, and hence remain in the blood circulation. Excretion of drugs excretion is defined as the process where by drugs or metabolites are irreversibly transferred from internal to external environment through renal or non renal route. Factors affecting drug absorption and distribution. Distribution, metabolism and excretion are sometimes referred to collectively as drug disposition.
Factors effecting bioavailability studies bodavula samba siva rao department of pharmacy, khammam college of pharmacy, khammam, andhra pradesh the goal of most oral dosage forms is to serve as a vehicle for the delivery of drugs to the blood stream for distribution to the site of action. The following factors can affect the blood concentrations of a drug. Additional factors affecting drug reabsorption include lipid solubility, drug size, and urine flow. This method is very effective if the drug is excreted in the unchanged form. Drugs are absorbed from the site of administration into the systemic circulation, where they may interact with the proteins. It can be slowed by coadministration of vasoconstrictors, a practice commonly used to prolong the local action of local anesthetics. Only relatively polar drugs are excreted in appreciable amounts by the kidneys. Excretion the interrelationship between drug distribution, biotransformation and excretion and the drug in figure 1. Pharmaceutical factors a chemical factors b physicochemical properties of drug substances 1. The proposed research will attempt to remedy this shortcoming by quantitating the effect of changes in renal blood flow, drug protein binding, drug concentration, aging, and several experimental disease states upon the renal clearance of model substrates in an isolated perfused rat kidney preparation iprk. Compare the roles of passive diffusion and carriermediated transport in drug absorption. Indiana universitypurdue university at indianapolis, indianapolis, in, united states. Factors affecting urinary excretion of testosterone metabolites conjugated with cysteine.
Limits gf but doesnt limit active tubular secretion 3. Feb 27, 2019 drug distribution is a subject that is covered in a branch of pharmacology called pharmacokinetics. Species differences have a major influence on the renal excretion of ionized drugs. Additional factors affecting drug reabsorption include lipid solubility, drug size, and. Factors contributing to variability in drug pharmacokinetics. Factors effecting on drug distribution ashok kari 1, gandhu sateesh, bharatha suresh, bodavula samba siva rao2 1. Factors affecting the urinary excretion of endogenously. Overview of factors affecting oral drug absorption naining song a,b, shaoy u zhang b, changxiao liu a a tianjin state key laboratory of pharmacokinetics and pharmaco dynamics, tianjin inst. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Pharmacokinetics definition, principles, factors affecting.
Drug absorption, drug distribution, drug dissolution, drug solubility introduction. Absorption is the process by which drugs enter the body. Pharmacokinetic is a quantitative study of drugs in the body absorption, distribution, metabolism and excretion of the law. A drug, which is either biologically active itself or a prodrug, may be excreted in its original chemical state. Genetic factors in drug metabolism american family physician. Impaired renal function may lead to a clinically significant accumulation of drugs eliminated by the kidneys, if more than 50% of the dose is normally excreted unchanged in the urine and the renal function is less than 50% of the normal value. Alternatively, all or a portion of a drug may undergo chemical modification and be eliminated as biologically active, or inactive, metabolites see the record on drug biotransformation. Drug excretion is the process of eliminating a drug from the body.
Drug absorption, nonrenal clearance, and volume of distribution of drugs are in fact altered by crf via changes in hepatic clearance, intestinal absorption and first pass metabolism, hepatic, renal, and intestinal transport, plasma protein binding, and tissue binding. Pdf overview of factors affecting oral drug absorption. The speed with which drugs move in and out of the body varies widely among different people. The effect of chronic renal failure on drug metabolism and. Factors governing the extent of drug absorbed from the mucosal surface include the concentration the active ingredient, the vehicle used for its delivery, contact time with the mucosal surface. Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be subdivided into internal physiological and pathological and. Acidification of urine increases reabsorption and decreases excretion of weak acids, and, in contrast, decreases reabsorption of weak bases. Because so many factors affect drug response, doctors must choose a drug appropriate for each person and must adjust the dose carefully. Overview of pharmacokinetics clinical pharmacology. Aug 14, 2017 there are four factors that will influence the pharmacokinetic drugs test.
With oral administration, several factors affect the absorption of a drug. There are four factors that will influence the pharmacokinetic drugs test. Factors influencing drug response intrinsic genetic. Physiological factors affecting absorption pharmatutor. The factors affecting absorption of drugs are related both to the drugs and to the body factors related to drugs. Lipid soluble compound metabolized into more polar compound eliminated. The drug distribution is usually varied, and depends on several factors such as. These factors may affect how the body absorbs the drug, how the body breaks down metabolizes and eliminates the drug, or what effects the drug has on the body. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in. Given by any route other than intravenously, drug molecules must cross tissue membranes e. The route of administration, dose, and condition of the animalto name a few factorscan have a profound effect on excretion rates. Feb 27, 2019 various factors can affect renal excretion, such as. Absorption can be facilitated by heat, massage or vasodilators.
Dhanvanthari institute of pharmaceutical sciences, kothagudem, khammam. Introduction to pharmacokinetics and pharmacodynamics. Pharmacodynamics, described as what a drug does to the body, involves receptor binding, postreceptor effects, and. In elderly patients, or those with chronic renal disease see the record on renal disorders including interstitial nephritis, glomerulonephritis, hypertensive nephrosclerosis, diabetic nephropathy, and polycystic kidney disease, renal function becomes progressively reduced such that drug excretion may become impaired. Many factors can affect a drug s absorption, distribution, metabolism, excretion, and ultimate effect. Thus making it difficult to determine its effects directly. Absorption, distribution, metabolism, and excretion. Large interindividual variations in drug response can arise from multiple genetic and environmental factors affecting drug absorption, distribution, biotransformation, excretion, interaction with receptor sites, or combinations of these. Some drugs are not affected by food, while the absorption of a third group of drugs is enhanced by food bile secretion by liver in response to food in gi tract increases drug absorption. Compare the roles of passive diffusion and carriermediated transport in. Many factors can affect a drugs absorption, distribution, metabolism, excretion, and ultimate effect. Intravenous administration does not involve absorption and, hence, there is no loss of drug. Explain how bioavailability can impact drug response and product selection. Greater the lipid water solubility coefficient, more is the lipid solubility of the drug and greater is the absorption.
Amount of drug that exists in unionized form and in ionized form is a function of pka of drug and ph of the fluid at the absorption site, and it can be determined by handersonhasselbach equation. Overview of pharmacokinetics clinical pharmacology merck. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal. Examples of genes affecting chd include the cholesteryl ester. Factors affecting the renal excretion of drugs stephen hall. List two physiologic factors that can alter each of the processes of absorption, distribution, and excretion. Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the bodythe time course of its absorption, bioavailability, distribution, metabolism, and excretion.
For most tissues, passive aqueous diffusion through channels. If we need to understand the basics we must be aware of the fact that drug effect in the body cannot be directly measured for e. Laboratory of chemical pharmacology, national heart and lung institute, national institutes of health bethesda, md. Factors affecting drug activity flashcards quizlet. Lipidsoluble drugs are absorbed rapidly while absorp.
Factors affecting pharmacokinetics of drugs medicilon inc. Factors affecting renal drug excretion glomerular filtration o drugs enter the kidney from the renal artery o glomerulus can be thought of as a spaghetti strainer spaghetti proteins is not filtered, whereas salt added to the spaghetti small molecules such as drugs or different ions are filtered. Some drugs are irritating and should be administered with meals to reduce adverse effects. Impaired renal function may lead to a clinically significant accumulation of drugs eliminated by the kidneys, if more than 50% of the dose is normally excreted unchanged in the urine and the renal function is less than 50% of the. Clinical pharmacokinetics is the application of pharmacokinetic principles to. In the first chapter, the principles underlying drug absorption, distribution, metabolism and elimination are described, with drug metabolism highlighted within the context of these fundamental processes. Various factors can affect renal excretion, such as. In elderly patients, or those with chronic renal disease see the record on renal disorders including interstitial nephritis, glomerulonephritis, hypertensive nephrosclerosis, diabetic nephropathy, and polycystic kidney disease, renal function becomes progressively reduced such that drug excretion may. Excretion drug excretion is defined as the removal of drugs from the body.
The use of mathematical principles and methods to explain the plasma concentration with time changes in a discipline. Transdermal administration, drug testing and analysis, 10, 5, 821831, 2017. Toxicants are removed in the kidney by glomerular filtration, tubular excretion by passive diffusion, and active tubular secretion. Factors affecting drug absorption and distribution request pdf. How a drug works and what happens to it upon entering the body are important factors in drug design, in order to ensure optimal action in the desired amount of time. Clinical pharmacokinetics pharmacology education project. Overview of response to drugs msd manual consumer version. If you continue browsing the site, you agree to the use of cookies on this website. Or excretion is defined as the process where by drugs or metabolites are irreversibly transferred from internal to external environment through renal or non renal route. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water. Unionized drugs and metabolites are usually able to diffuse out of the renal tubule and are reabsorbed into the blood.
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